Infusion of haplo-identical killer immunoglobulin-like receptor ligand mismatched NK cells for relapsed myeloma in the setting of autologous stem cell transplantation.
Killer immunoglobulin-like receptor (KIR)-ligand mismatched natural killer (NK) cells play a key role in achieving durable remission after haplo-identical transplantation for acute myeloid leukaemia. We investigated the feasibility of transfusing haplo-identical, T-cell depleted, KIR-ligand mismatched NK cells, after conditioning therapy with melphalan and fludarabine, to patients with advanced multiple myeloma (MM) followed by delayed rescue with autologous stem cells. No graft-versus-host disease or failure of autologous stem cells to engraft was observed. There was significant variation in the number of allo-reactive NK cells transfused. However, all NK products containing allo-reactive NK cells killed the NK cell target K562, the MM cell line U266, and recipient MM cells when available. Post NK cell infusion there was a rise in endogenous interleukin-15 accompanied by increasing donor chimaerism. Donor chimaerism was eventually lost, which correlated with the emergence of potent host anti-donor responses indicating that the immunosuppressive properties of the conditioning regimen require further optimization. Further, blocking of inhibitory KIR-ligands with anti-human leucocyte antigen antibody substantially enhanced killing of MM cells thus highlighting the potential for modulating NK/MM cell interaction. Encouragingly, 50% of patients achieved (near) complete remission. These data set the stage for future studies of KIR-ligand mismatched NK cell therapy in the autologous setting.
Shi
Jumei
J
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Tricot
Guido
G
Szmania
Susann
S
Rosen
Nancy
N
Garg
Tarun K
TK
Malaviarachchi
Priyangi A
PA
Moreno
Amberly
A
Dupont
Bo
B
Hsu
Katharine C
KC
Baxter-Lowe
Lee Ann
LA
Cottler-Fox
Michele
M
Shaughnessy
John D
JD
Barlogie
Bart
B
van Rhee
Frits
F
D000328:Adult; D000368:Aged; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D054340:Receptors, KIR / Q000276:immunology*; D012008:Recurrence; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D008024:Ligands; D054340:Receptors, KIR